SCN1A , encoding the alpha 1 subunit of the voltage-gated sodium channel Nav1.1, is associated with a wide clinical spectrum of epilepsies ranging from genetic epilepsy with febrile seizures plus (GEFS+), to developmental and epileptic encephalopathies (DEEs). Dravet syndrome (DS) is the prototypic DEE presenting with recurrent, often prolonged febrile and afebrile seizures, including hemiclonic, generalized tonic-clonic seizures and status epilepticus. Subsequently other seizure types, such as myoclonic and atypical absence seizures, emerge as well as long-term problems with learning, motor development and behaviour. In contrast, individuals with GEFS+ phenotypes have well controlled epilepsy with normal cognition. Apart from epilepsy, SCN1A has also been associated with familial hemiplegic migraine, a subtype of migraine with aura characterised by hemiparesis during the attacks.
DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development
DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development
DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development
DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development
DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development
DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development
SCN2A -related disorders are characterized by a wide clinical spectrum ranging from benign familial infantile seizures to developemental and epileptic encephalopathy. Furthermore, SCN2A is one of the most prominent monogenic causes of autism spectrum disorders. Variants causing both gain and loss of function have been identified as the underlying pathomechanism. Correlations between functional outcome and clinical phenotype includes: autism and/or late onset epilepsy for individuals with loss of function variants and neonatal onset self-limiting epilepsy or neonatal/infantile DEE with gain of function variant. As subset of individuals with self-limiting epilepsy develop episodic ataxia later in childhood.
DEE: Developmental epileptic encephalopathy
DEE: Developmental epileptic encephalopathy
DEE: Developmental epileptic encephalopathy
DEE: Developmental epileptic encephalopathy
DEE: Developmental epileptic encephalopathy
SCN3A -related disorders are characterized mainly by epilepsy often associated with brain malformations such as polymicrogyria (abnormal gyration of the brain). Affected individuals often have intellectual disability. Seizure types varies, and includes focal, febrile, myoclonic and tonic seizures among others. Functional studies have revealed both gain and loss of function as underlying pathomechanism. Because of a small number of known affected individuals, correlations between functional outcome, genotype and phenotype are still sparse. The limited data there is, suggests that brain malformations are mainly seen in individuals with gain of function variants, while epilepsy and intellectual disability are seen in both individuals with gain and loss of function variants.
GEFS +: Generalized epilepsy with febrile seizures plus; DEE: Developmental and Epileptic Encephalopathies; PMG: Polymicrogyria; ASD: Autism spectrum disorder
GEFS +: Generalized epilepsy with febrile seizures plus; DEE: Developmental and Epileptic Encephalopathies; PMG: Polymicrogyria; ASD: Autism spectrum disorder
SCN8A, encoding the alpha subunit of the voltage-gated sodium channel Nav1.6, is associated with a wide clinical spectrum of epilepsies ranging from benign familial infantile seizures (BFIS), over an intermediate phenotype with treatable seizures and mild-moderate intellectual disability, to severe developmental and epileptic encephalopathies (DEEs). SCN8A-DEE is characterized by early onset intractable seizures, cognitive impairment, movement disorders, cortical visual impairment and severe gastrointestinal symptoms. The seizures are often prolonged focal hypomotor and occur in clusters, with prominent vegetative symptoms, evolving to clonic or bilateral tonic-clonic manifestations. Spasm-like episodes, cortical myoclonus, and recurrent episodes of status epilepticus are also common. In contrast, individuals with BFIS have well controlled self-limiting epilepsy with no other neurological deficits and normal cognition. In addition, rare clinical presentations with ID, autism spectrum disorder and movement disorders without epilepsy have been described.
DEE: Developmental and Epileptic Encephalopathies; BFIE: Benign Familial Infantile Epilepsy; GGE: Genetic Generalized Epilepsy; IE: Intermediate Epilepsy; UE: Unclassifiable Epilepsy; NDDwoe: Neurodevelopmental Disorder without Epilepsy
DEE: Developmental and Epileptic Encephalopathies; BFIE: Benign Familial Infantile Epilepsy; GGE: Genetic Generalized Epilepsy; IE: Intermediate Epilepsy; UE: Unclassifiable Epilepsy; NDDwoe: Neurodevelopmental Disorder without Epilepsy
DEE: Developmental and Epileptic Encephalopathies; BFIE: Benign Familial Infantile Epilepsy; GGE: Genetic Generalized Epilepsy; IE: Intermediate Epilepsy; UE: Unclassifiable Epilepsy; NDDwoe: Neurodevelopmental Disorder without Epilepsy
If your family has received a diagnosis of an SCN-related neurodevelopmental disorder, you've probably never heard of it before. That's okay. Your doctors probably haven't either! But the Educational Science community is here to help.
In this section, you can find a series of short explainer videos that are designed to help patients, families, and clinicians to learn about SCN-related neurodevelopmental disorders in plain language. Over time, we'll be adding more content to cover all SCN genes and related topics.
The series starts with an overview video about all SCN-genes included in this Portal:SCN1A, SCN2A, SCN3A, SCN8A.
Next, we present a comprehensive video on SCN1A-related disorders and introductory video on SCN2A-related disorders.
From this videos you'll learn:Transcripts: SCN1A: NM_001165963.4, SCN2A: NM_001040142.2, SCN3A: NM_006922.4, SCN8A: NM_001330260.2
The SCN Portal is a coalition of investigators seeking to aggregate and harmonize data generated to study SCN-related disorders, and to make summary data interactively accessible for the wider scientific community, while providing educational resources for everyone. The goals of this project are:
Andreas Brunklaus (Glasgow, UK): SCN1A Clinical & genetic data
Stephanie Schorge (London, UK): Functional data curation
Rikke Møller (Dianalund, DK): SCN1A , SCN2A , SCN8A Clinical & genetic data
Ingo Helbig (Philadelphia, US): SCN2A Clinical & genetic data
Jen Q Pen (Cambride, US): SCN2A High-throughput functional data
Alfred George (Chicago, US): SCN1A & SCN2A High-throughput functional data
Dennis Lal (Cleveland, US): General concept, web development, bioinformatics, video production
Katrine Johannesen
Ingo Helbig
Sameer Zuberi
Holger Lerche
Massimo Mantegazza
Sandrine Cestele
Tobias Brünger
Arthur Stefanski
Chiara Klöckner
Marie Mcnee
Tobias Brünger
Eduardo Perez-Palma
Chiara Klöckner
Tobias Brünger
Eduardo Perez-Palma
Marie Mcnee
Patrick May
Arthur Stefanski
Alina Ivaniuk
Andreas Brunklaus
Katrine Johannesen
Mary Anne Meskis : SCN1A
Veronica Hood : SCN1A
Leah Schust : SCN2A
We object to any commercial use and disclosure of data.
Copyright and use: The authors grants you the right of use to make a private copy for personal purposes. However, you are not entitled to change and/or pass on the materials or publish them yourself. Upon request, you will receive free information about the personal data stored about you. To do so, please contact the administrator.
No liability: The contents of this web project have been carefully checked and created to the best of our knowledge. But for the information presented here is no claim to completeness, timeliness, quality and accuracy. No responsibility can be accepted for any damage caused by reliance on or use of the contents of this website.
All data here are publicly for the benefit of the wider biomedical community. You can freely explore the data, and we encourage the use and publication of results generated from these data. However, we encourage you to
contact us
before embarking on analyses to check if your proposed analysis overlaps with our team's current work. Further, we request that you actively acknowledge and give attribution to the SCN Portal project and link back to the relevant page, wherever possible. All users of our data agree not to attempt to reidentify participants. Our data set has been subjected to extensive quality control but may be imperfect so that errors may remain.
If you spot any results that seem impossible or have suggestions for SCN Portal improvements:
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so that we can improve.